Integrated pipette tip devices

ABSTRACT

Disclosed herein are fluid handling devices that include integrated card and pipette tip devices, for use with multichannel liquid dispensing devices.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/320,177, filed Jun. 30, 2014. now U.S. Pat. No. 9,302,262, entitled“Integrated Pipette Tip Devices” naming Arta Motadel et al as inventors,which is a continuation of U.S. patent application Ser. No. 13/484,220,filed May 30, 2012, now U.S. Pat. No. 8,795,606, entitled “IntegratedPipette Tip Devices” naming Arta Motadel et al. as inventors. The entirecontent of the foregoing patent application is incorporated herein byreference, including all text tables and drawings.

FIELD OF THE TECHNOLOGY

The present technology relates in part to pipette tip devices that canbe utilized with multichannel liquid dispenser devices.

BACKGROUND

Pipette tips are ubiquitous tools of many research laboratories and offacilities in which small volumes of liquid are handled. Liquiddispensers sometimes are manually operated by a user and sometimes areautomated. Liquid dispensing devices often are operated in conjunctionwith pipette tips, where pipette tips are sealingly connected to thedispensing device, the dispensing device applies negative or positivepressure in the interior of the pipette tips and liquid enters or exits,respectively, the pipette tips.

As laboratory and clinical technologies advance, an increasing number ofmedical and laboratory procedures are performed by high throughputmanual and automated processes. Many of these laboratory or clinicalprocesses and procedures are carried out using pipette tips inconjunction with multichannel dispensing devices (e.g., also known asmultichannel pipettors). Multichannel dispensers are currently availablewith as few as 4 channels (e.g., hand held manually operated pipette) orsometimes as many as 1536 channels (e.g., automated high throughputbiological workstations).

Pipette tips generally are held in a tray, rack or holder, and orientedsubstantially vertically for presentation of the tips for use by anoperator. The tips are held in a card of the rack in a verticalorientation such that the proximal portion of the pipette tips can beengaged by the dispenser nozzles or channels. A rack often comprisesfour sides, and optionally contains a grid structure within the bodythat confers rigidity to the rack component. Pipette tip racks,available in configurations that can hold from approximately about 96 toabout 1536 tips, can be purchased commercially. Each pipette tip oftenis separated in a rack, and can be utilized individually or in a groupof other pipette tips. Pipette tips often are manually loaded into rackor holder devices for sterilization, storage, and ultimate use.

SUMMARY

Provided herein are devices that comprise pipette tips integrated with acard (e.g., co-extensive with, molded or thermoformed to, or connectedto a card). These devices are referred to herein as “integrated pipettetip devices.”

In certain aspects, provided is a two-piece integrated pipette tipdevice, including: a card in connection with a plurality of integratedpipette tips and a gasket in sealing connection with a first surface ofthe card, which card and pipette tips are constructed from a firstmaterial and the gasket is constructed from a second material relativelymore resilient than the first material; each of which pipette tipsincludes a distal region and each pipette tip extends from a secondsurface of the card opposite the first surface; which gasket includes asurface in connection with the first surface of the card, which surfaceof the gasket covers about 80% or more of the first surface of the card(e.g., about 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100% of the firstsurface of the card); which card includes card apertures definingchannels that traverse the thickness of the card, each of which cardapertures is concentric with one pipette tip; and which gasket includesgasket apertures that traverse the thickness of the card, each of whichgasket apertures is concentric with one card aperture.

Provided also in some aspects is an integrated pipette tip device,including: a substantially flat card including a first surface and anopposing second surface, which card includes a plurality of apertures,each aperture defining the opening of a channel traversing the thicknessof the card; which card includes a plurality of integrated pipette tips,each of which pipette tips including a distal region that effectivelyextends from the second surface of the card and is concentric with oneaperture; and which card includes a plurality of bores, each of whichbores having an opening on the first surface of the card located at theintersection of four adjacent apertures, and which bores extend throughat least a portion of the thickness of the card.

In certain aspects, also provided is an integrated pipette tip device,including: a substantially flat card including a first surface and anopposing second surface, which card includes a plurality of apertures,each aperture defining the opening of a channel traversing the thicknessof the card; which card includes a plurality of integrated pipette tips,each of which pipette tips including a distal region that effectivelyextends from the second surface of the card and is concentric with oneaperture; and which card includes a plurality of dispenser sealingmembers, each of which sealing members including an opening in effectiveassociation with one channel of the card, and each of which sealingmembers (i) is in connection with the second surface of the card and thedistal region of a pipette tip, or (ii) is in effective connection withthe first surface of the card and includes one or more sealing memberribs, one or more sealing member depressions, a flange, a flexiblematerial not present in the card or pipette tips, or combinationthereof.

Provided in some aspects is an integrated pipette tip device, including:a substantially flat card including a first surface and an opposingsecond surface, which card includes a plurality of apertures, eachaperture defining the opening of a channel traversing the thickness ofthe card; which card includes a plurality of integrated pipette tips,each of which pipette tips including a distal region that effectivelyextends from the second surface of the card and is concentric with oneaperture; and which card includes a plurality of pipette tip supportribs, each of which pipette tip support ribs is in connection with onepipette tip and the second surface of the card.

In certain aspects, provided is a device provided herein is in sealingconnection with a gasket, which gasket includes apertures concentricallyaligned with the apertures in the device, which gasket is relativelymore resilient than the card of the device, and the surface of thegasket in connection with the first surface of the card covers about 80%or more of the first surface of the card. Provided in some aspects is amethod for dispensing a fluid by an integrated pipette tip device,including: engaging a dispensing device with an integrated pipette tipdevice described herein, drawing a fluid into the pipette tips of theintegrated pipette tip device, and dispensing the fluid from the pipettetips. In certain aspects, also provided is a mold configured tomanufacture an integrated pipette tip device described herein.

As addressed above, an integrated pipette tip device sometimes includesa sealing member, and a sealing member sometimes is referred to hereinas a “collar.” A sealing member sometimes is in connection with thefirst surface or the second surface of the card. A sealing membersometimes is in connection with a pipette tip distal region and often isin effective connection with a channel of the card (e.g., the sealingmember is in vacuum connection with a channel). An interior surface of asealing member sometimes defines a cylindrical or frustrum-shaped void.An interior surface of a pipette tip, e.g., pipette tip distal region,often defines a cylindrical or frustrum-shaped void. An interior surfaceof a sealing member also sometimes defines a cylindrical orfrustrum-shaped void.

Certain embodiments are described further in the following description,claims and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate certain non-limiting embodiments of thetechnology. For clarity and ease of illustration, drawings are notnecessarily to scale, and in some instances, various elements may beshown exaggerated or enlarged to facilitate an understanding ofparticular embodiments.

FIG. 1A illustrates exploded and combined profile views of a two-pieceintegrated pipette tip device. FIG. 1B shows a top view of the gasketportion of a two-piece integrated pipette tip device. FIG. 1C shows abottom view of the gasket portion of a two-piece integrated pipette tipdevice. FIG. 1D shows a top view of the card portion of a two-pieceintegrated pipette tip device. FIGS. 1E and 1F show alternatecross-sectional views taken along the line labeled 1E/1F in FIG. 1A.FIGS. 1E and 1F illustrate enlarged views of the internal detail ofalternate embodiments of an assembled two-piece device.

FIG. 2A illustrates a profile view of a one-piece device embodiment.FIG. 2B shows a top view of a one-piece device embodiment illustratingbore or “cutout” regions, which are regions of material thinning orremoval in the card portion of the device. Alternate cross-section viewsof bores or regions of material thinning are illustrated in FIGS. 2C and2D. Each bore often has an opening on the first surface of the cardlocated at the intersection of four adjacent apertures, which fouradjacent apertures often are located at the points of a virtualrectangle or square imaged on the first surface of the card. The centerpoint of such a virtual rectangle or square often is coextensive withthe center point of the bore opening. FIG. 2E illustrates an alternatetop view of FIG. 2B showing optional annular ring protrusions from theupper surface of the card around the cylindrical apertures of the card.FIG. 2F illustrates a cross-section view of one of the cylindricalapertures surrounded by a depression in a protruding annular ring shownin FIG. 2E. In certain embodiments, the cylindrical channel of thepipette tip portion is alternatively a tapered channel having a frustumshape that engages a dispensing nozzle of a dispensing device (notshown).

FIG. 3A illustrates a profile view of a one-piece device embodimenthaving reinforcing ribs. FIG. 3B illustrates a profile view of aone-piece device embodiment with reinforcing ribs interconnectingadjacent pipette tips. FIG. 3C shows a top view of the one-piece devicesillustrated in FIGS. 3A and 3B.

FIG. 4A to FIG. 4G show cross section views of device embodimentshaving, or configured to incorporate, substantially resilient sealingelements. FIG. 4H shows a top view of such device embodiments.

FIG. 5A illustrates a profile view of a one-piece device embodimenthaving proximal collars, or sealing members, extending from theunderside of the card. The tapered or frustum shaped distal portion ofeach device extends from a proximal collar region. FIG. 5A illustratesalternate proximal collar configuration embodiments. FIGS. 5B and 5Cillustrate certain bottom views of the one-piece device embodimentsshown in FIG. 5A. The alternate proximal collar embodiments also areshown in FIGS. 5B and 5C. FIG. 5C illustrates an embodiment includingsubstantially diamond shaped bores configured to allow increasedflexibility of the collar sealing member during dispenser nozzleengagement and disengagement.

FIG. 5D illustrates a profile view of a device embodiment havingproximal collars and various reinforcing rib embodiments. Reinforcingrib embodiments shown in FIG. 5A are substantially similar to ribembodiments illustrated in FIG. 3A. FIG. 5E illustrates a profile viewof a device with proximal collars and reinforcing ribs interconnectingadjacent pipette tips. Reinforcing rib embodiments shown in FIG. 5E aresubstantially similar to rib embodiments illustrated in FIG. 3B.

FIG. 6A, FIG. 6B and FIG. 6C show side views of various integratedpipette tip device embodiments that include sealing members comprisingribs and/or depressions, which sealing members are in connection withthe first surface of the card.

DETAILED DESCRIPTION

Laboratories are taking greater advantage of automated and highthroughput procedures, and the density of pipette tips utilized incertain applications has increased. For example, multiwell plates oftenare utilized in high throughput procedures and the plates often arepaired with racks having cards that present a number of pipette tipsequal to the number of wells in a multiwell plate. For example, where 96well multiwell plates have been utilized, 384 well plate and 1536 wellplate formats presently are in use, which has given rise to pipette tiptrays that present 384 and 1536 pipette tips corresponding to the numberof wells in the multiwell plates. Pipette tips loaded in 384 tip traysare smaller in size than pipette tips loaded in 96 tip trays, andpipette tips loaded in 1536 tip trays are smaller yet than pipette tipsloaded in 384 tip trays. The top surface of a pipette tip rack thatholds and presents the pipette tips, which sometimes is referred to as a“card” or “snap plate,” generally does not increase in surface area when96, 384 or 1536 pipette tips are presented, as industry standardsregulate and define the length and width dimensions of the rack and snapplate. This limit on snap plate and rack dimensions gives rise to anincreased surface density of pipette tips as a greater number of pipettetips are presented by pipette tip racks.

Increased pipette tip density in a rack sometimes can cause an increasedfrequency of problems with the preparation of and/or used of pipettetips in pipette tip storage racks, including, for example, (i) anincreased probability that pipette tips are not perfectly aligned in theracks (e.g., not aligned with an axis perpendicular to the snap plate),which can lead to poor seals when the pipette tips are engaged with adispensing device and inaccurate and imprecise dispensing volumes; and(ii) an increased effort associated with loading smaller tips, which aremore challenging to manipulate, into racks, which can lead to repetitivemotion injuries and elevated costs.

Pipette tips also may deviate from substantially vertical alignment instorage boxes due to static charge. Static charge is another challengethat has arisen due to the close packing of smaller, narrower tips instorage units that have remained roughly the same size. As mentionedabove, storage units have remained roughly the same size, yet 4 to 16times as many tips sometimes are stored therein. This significantincrease in the number of tips has resulted from the tips being moreclosely packed, which in turn may allow the tips to make contact witheach other in the storage units. The contact between the tips in thestorage unit, can lead to the build up of static charge. Due to the tipsbeing constrained in the storage boxes, the static charge can act as arepulsive force between tips in the storage unit. The repulsive force inturn can cause a deviation from vertical alignment of the tips in thestorage unit, and thus cause a deviation from concentricity of thepipette tips with respect to the engaging dispenser nozzle. If the tipsand nozzles are not substantially axially aligned, the dispenser nozzlesmay not engage the tips properly, leaving nozzles with improperlyengaged pipette tips (e.g., tips that may not seal properly), and, insome instances, no pipette tip at all.

In some instances, electrostatic forces (e.g., static charge) also maybe transferred from the pipette tips to a human user handling the tipsthemselves or with a dispensing device. The static charge also maydischarge a shock to samples or specimens the tips come into contactwith, which may distort the accuracy of assays being performed.Microscopic specimens, C. elegans for example, may be highly affected bythe slightest electrostatic force. Additionally, highly sensitiveequipment, such as meters, may be effected by static charge and suchdelicate machinery is oftentimes found in laboratories or settings usingmultichannel dispensers and pipette tips.

Manual loading of pipette tips into racks and holders represents abottleneck in the ability to rapidly load tips into holders forpreparation, storage and use. In particular, the increase in number ofpipette tips, by 4 or 16 times, means 4 or 16 times more repetitivemotions (e.g., manual placement of tips in pipette tip holders) perstorage unit. Repetitive motion can adversely bear on the health ofoperators. Increasing the probability of such injuries, coupled with thecost associated with the time-intensive nature of such activities,ultimately drives costs upward for the overall processes.

Integrated pipette tip devices described herein provide advantageousbenefits that reduce or eliminate problems associated with (i) loss ofconcentricity, (ii) static charge build-up, and/or (iii) repetitivemotion injuries. Devices presented herein reduce or eliminatedifficulties associated with manufacture, loading and storage of pipettetips for multichannel liquid dispensers having 96 or more channels. Forexample, integrated pipette tip devices described herein reduce oreliminate the loss of concentricity on a central axis shared between thedispenser nozzle and pipette tip proximal portions that the dispensernozzles engage. Lack of concentricity can be caused by static chargebuild up in storage units or by shaking or jostling of the storageunits. Integrated pipette tip devices reduce or eliminate the loss ofconcentricity of a shared central axis by constraining the proximalportions of all the tips on a card or plate, and thereby limiting orabrogating lateral movement of the dispenser-engaging openings, in someembodiments.

Integrated pipette tip devices described herein reduce or eliminatedeviations in concentricity of upper and lower openings and a centralaxis by providing reinforcing ribs, in certain embodiments. In certainembodiments, the reinforcing ribs can prevent (i) lateral movement andpivoting of tips when the tips are engaged with a dispenser, and (ii)pipette tip wall curvature sometimes associated with the manufacture ofsmaller pipette tips having the thinner walls necessary for use with thethinner dispensers of multichannel dispensers having 96 or morechannels. In some embodiments, integrated pipette tip devices also canreduce or eliminate costs associated with potential repetitive motioninjury hazards arising from manually loading pipette tips into storageunits (e.g., particularly units designed for 384 or 1536 pipette tips),by integrating tips on a card that fits into standard storage units andeliminates the need for individual placement of tips into holders.

Integrated pipette tip devices provided herein (i) stabilize pipettetips, and reduce or prevent lateral movement and/or pivoting of tipswhen they are engaged with a dispenser; (ii) promote efficient sealingof the pipette tips to a dispenser; (iii) reduce or eliminate thepotential for repetitive motion injuries, as multiple pipette tips areloaded in one motion into a rack; (iv) are of relatively simple designsthat can be readily manufactured (e.g., injection molded) withrelatively small amounts of material; (v) provide pipette tips ofsubstantially regular dimensions and/or geometries; and (vi) reduce orabrogate electrostatic charge that can be generated on or in pipettetips that are not integrated with a card. These features can provideadvantageous benefits, including, for example, improved accuracy andprecision for liquid volumes delivered by integrated pipette tipdevices.

Integrated pipette tip devices can be configured as two-piece orone-piece devices. In general, the card portion (also referred to as asnap plate or pipette tip snap plate) has a substantially similarconfiguration in one-piece and two-piece integrated pipette tip devices.The card portion often has substantially similar dimensions (e.g.,length, width, thickness), can be made of the same materials, and can bemanufactured in the same manner, for one-piece and two-piece devices.Additionally, for cards with similar numbers of pipette tips (e.g., 96,384, or 1536 pipette tips) the dimensions between tips (e.g., center tocenter spacing of tips), and the manner in which the tips are arrayed,often are substantially similar between one-piece and two-piececonfigurations with the same number of tips.

Materials useful for manufacturing devices and components (e.g. moldableplastics, moldable thermoplastic elastomers, anti-static oranti-microbial additives and the like, for example), as well asdimensions of various aspects of the tips (e.g., center to centerdistances between tips, length of tips, and the like, for example) aredescribed herein. Card members in integrated pipette tip devices canhave a thickness between about 0.5 to about 5 milliliters, in certainembodiments. Card members in integrated pipette tip devices can have athickness about 0.5 millimeters, about 0.6 millimeters, about 0.7millimeters, about 0.8 millimeters, about 0.9 millimeters, about 1.0millimeter, about 1.1 millimeters, about 1.2 millimeters, about 1.3millimeters, about 1.4 millimeters, about 1.5 millimeters, about 1.6millimeters, about 1.7 millimeters, about 1.8 millimeters, about 1.9millimeters, about 2.0 millimeters, about 2.1 millimeters, about 2.2millimeters, about 2.3 millimeters, about 2.4 millimeters, about 2.5millimeters, about 2.6 millimeters, about 2.7 millimeters, about 2.8millimeters, about 2.9 millimeters, about 3.0 millimeters, about 3.1millimeters, about 3.2 millimeters, about 3.3 millimeters, about 3.4millimeters, about 3.5 millimeters, about 3.6 millimeters, about 3.7millimeters, about 3.8 millimeters, about 3.9 millimeters, about 4.0millimeters, about 4.1 millimeters, about 4.2 millimeters, about 4.3millimeters, about 4.4 millimeters, about 4.5 millimeters, about 4.6millimeters, about 4.7 millimeters, about 4.8 millimeters, about 4.9millimeters, or about 5.0 millimeters, in some embodiments.

A pipette tip in devices described herein typically has an upper andlower opening, where the upper opening of a pipette tip proximalopening) may be engaged with a dispensing device, and the lower openingof a pipette tip (distal opening) typically contacts liquid. The upperand lower openings of a pipette tip typically have concentric centers.The terms “concentricity” or “co-centricity”, and grammatical variantsthereof, as used herein, refers to two or more shapes (e.g., circles,for example) having a common center.

Two-Piece Devices and Methods of Use

In some embodiments a two-piece integrated pipette tip device 10includes an integrated card 16 in connection with a plurality of pipettetips 18 and a gasket 12 in sealing connection with a first surface 20 ofthe card 16, as illustrated in FIG. 1A. FIG. 1A illustrates two-pieceintegrated pipette tip device 10, in exploded and assembled views. Thecard portion of two-piece integrated pipette tip device 10 (andone-piece integrated card devices described below) can also be referredto as a “snap plate”, “snap card”, “card” or “integrated pipette tipcard”, throughout the document.

Gasket 12 is configured to be substantially similar in size and shape tothe card portion of two-piece card configuration 10. Gasket 12 can beconfigured to have substantially the same planar shape and surfacedimensions as card 16. Gasket 12 can be substantially rectangular inshape, where the length of a side can be between about 120 to about 140millimeters, and more specifically between about 125 to about 135millimeters in some embodiments (e.g., about 120 millimeters, about 125millimeters, about 126 millimeters, about 127 millimeters, about 128millimeters, about 129 millimeters, about 130 millimeters, about 131millimeters, about 132 millimeters, about 133 millimeters, about 134millimeters, about 135 millimeters, or about 140 millimeters). Gasket 12can range in thickness from about 0.5 to about 3 millimeters (e.g.,about 0.5 millimeters, about 0.6 millimeters, about 0.7 millimeters,about 0.8 millimeters, about 0.9 millimeters, about 1.0 millimeter,about 1.1 millimeters, about 1.2 millimeters, about 1.3 millimeters,about 1.4 millimeters, about 1.5 millimeters, about 1.6 millimeters,about 1.7 millimeters, about 1.8 millimeters, about 1.9 millimeters,about 2.0 millimeters, about 2.1 millimeters, about 2.2 millimeters,about 2.3 millimeters, about 2.4 millimeters, about 2.5 millimeters,about 2.6 millimeters, about 2.7 millimeters, about 2.8 millimeters,about 2.9 millimeters, or about 3.0 millimeters).

The upper surface of a gasket embodiment is illustrated in FIG. 1B. Agasket 12 can have an array of apertures (e.g., openings) 26 that definea channel that traverses the thickness of the gasket. The lower surfaceof a gasket embodiment is illustrated in FIG. 10. FIG. 10 shows thebottom of the array of channels terminating in apertures 26. FIG. 10also shows annular protrusions 28, illustrated as 14 in the profile viewpresented in FIG. 1A, which are optional.

In some embodiments the lower surface of gasket 12 (FIG. 10) is inconnection with the first surface of card 16, and covers about 80% ormore of the first surface of card 16. Gasket 12 covers about 80% ormore, about 85% or more, about 90% or more, about 95% or more, or about100% of the first surface of card 16 in some embodiments. In certainembodiments, gasket 12 may have annular protrusions 14, 14′ (see FIGS.1E and 1F), which protrude from the lower surface of the gasket (e.g.,the surface in contact with card 16), and annular protrusions 14, 14′are in contact with the first surface of card 16. The height thatannular protrusions 14, 14′ (FIG. 1A) and 28 (FIG. 10) protrude belowthe lower surface of gasket 12 can be in the range of about 0.1 to about1.0 millimeters (e.g., about 0.1 millimeters, about 0.2 millimeters,about 0.3 millimeters, about 0.4 millimeters, about 0.5 millimeters,about 0.6 millimeters, about 0.7 millimeters, about 0.8 millimeters,about 0.9 millimeters, about 1.0 millimeter). In some embodiments,protrusion 14, 14′ of gasket 12 is in contact with an inner surface ofbore 19′ at the interface where gasket 12 and card 16 are in physicalcontact (see FIG. 1F).

In some embodiments, annular protrusions around apertures in the card,on the top surface of the card (see FIG. 1D), can engage apertures in agasket (e.g., a gasket having no annular protrusions) and form a sealbetween the gasket and the card. In certain embodiments, annularprotrusions around apertures in the card, on the top surface of the card(see FIGS. 2E, 2F, and 3C) can engage a surface of a dispenser nozzleholder and form a seal between the dispenser nozzle holder and the card.In some embodiments the height of the annular protrusions range betweenabout 0.25 millimeters to about 2.0 millimeters in some embodiments(e.g., about 0.25 millimeters, about 0.3 millimeters, about 0.35, 0.4millimeters, about 0.45 millimeters, about 0.5 millimeters, about 0.6millimeters, about 0.7 millimeters, about 0.8 millimeters, about 0.9millimeters, about 1.0 millimeter, about 1.1 millimeters, about 1.2millimeters, about 1.3 millimeters, about 1.4 millimeters, about 1.5millimeters, about 1.6 millimeters, about 1.7 millimeters, about 1.8millimeters, about 1.9 millimeters, or about 2.0 millimeters).

In some embodiments, one, two or more surfaces (e.g., all surfaces) ofthe gasket may be substantially flat (e.g., the bottom surface of thegasket may be flat and incorporate annular protrusions aroundapertures). In certain embodiments, gasket 12 can be made from amaterial that is relatively more resilient than the material used tomake devices described herein. In some embodiments, the relatively moreresilient material may be a moldable thermoplastic elastomer. In certainembodiments, the relatively more resilient material of the gasket mayhave absorptive properties.

Integrated card 16 (FIG. 1A), has first and second surfaces, 20 and 22,respectively. The first surface 20 of card 16 also can be referred to asthe upper surface while the second surface 22 also can be referred to asthe lower surface. The first and second surfaces of the card often aresubstantially planar in shape and often are substantially parallel toeach other. Card 16 is integrated with pipette tips 18. A distal regionof each pipette tip 18 can extend from the second surface 22 of card 16,opposite the first surface 20. In some embodiments, each pipette tip 18extends from a substantially vertical sealing member (e.g., ribbed ornon-ribbed dispenser tip engagement zone) that extends from a secondsurface 81 of card 80, as shown in FIG. 5A. In certain embodiments thesealing member contributes up to ⅓ the total length of the pipette tipextending from a second surface 81 of card 80 (or second surface 22 ofcard 16). In certain embodiments, the substantially vertical sealingmember includes ribs and/or depressions, and in some embodiments theribs include two or more alternating sets of ribs where each set of ribshas a thickness (e.g., a first thickness, a second thickness, a thirdthickness, and the like). Ribs may be of the same thickness and length,or of differing thickness and/or length, and sometimes alternate ribs(the next rib) have a different thickness and/or length. Non-limitingexamples of ribbed sealing members suitable for use in devices describedherein can be found in published U.S. patent application 20110183433,incorporated herein in its entirety by reference.

The upper surface 20 of card 16 is illustrated in FIG. 1D. Card 16 oftenincludes an array of apertures 30, each of which apertures 30 form theopening of a channel that traverses the thickness of the card. Incertain embodiments, the channel opening forms a substantially 90 degreeedge, or forms a bevel, with surface 20 of the card. In certainembodiments, the aperture includes an edge feature, which oftensurrounds the aperture. Non-limiting examples of edge-features include aprotrusion or depression that transitions to the aperture edge by asurface defined by a right angle, radius, bevel, concave radius, convexradius, the like and combinations thereof. In some embodiments, card 16may have annular protrusions or depressions 32 extending or recessingfrom first surface 20, surrounding each of the apertures 30 in card 16.In some embodiments, apertures in the card are surrounded by noprotrusion, no depression, a radius, depression, the like, orcombination thereof. Apertures, protrusions, depressions and channelcross sections can be of any suitable shape (e.g., circular, annular,ovoid, rectangular, square, rhomboid and the like). Card depression andprotrusion embodiments also are shown in FIG. 4A to FIG. 4H.

The apertures in card 16 and apertures in gasket 12 often are concentric(e.g. card aperture 30 is coaxially aligned with gasket aperture 26(which axis extends through the proximal and distal pipette tipregions), and the apertures often are concentrically aligned with thedistal region cross section of each pipette tip 18. In some embodiments,gasket annular protrusions 14, 28 (different views of the sameprotrusions) surrounding gasket apertures 26, sealingly engage an innersurface of card apertures 30. In certain embodiments card annularprotrusions 32 surround card apertures 30 and sealingly engage an innersurface of gasket apertures 26. In certain embodiments, card annulardepressions 32 surround card apertures 30 and engage protrusions 14, orlike protrusions, in gasket 12. In some embodiments, apertures 30 incard 16 traverse the thickness of the card and can be in connection withthe interior volume of a distal region of pipette tips 18. In someembodiments, the reinforcing ribs described below (or the one-pieceintegrated pipette tip devices described below) can be incorporated inthe card piece of two-piece integrated pipette tip devices. FIGS. 1E and1F show enlarged views of a single pipette tip from assembled two-pieceintegrated pipette tip device embodiments. In some embodiments, asillustrated in FIG. 1E, upper surface 20 of card 16 can have depressionsconcentric with, and configured to be sealingly engaged by, annularprotrusion 14, 14′ of gasket 12. In some embodiments, a depression 32 incard 16 may facilitate seating and/or sealing of the gasket on the uppersurface 20 of the card (e.g., be seating a protrusion 14 of the gasket),and/or can allow proper orientation and subsequent engagement by adispenser channel. In the embodiment illustrated in FIG. 1E, the centralchannel 19, through which the dispenser channel enters and engages thetwo-piece integrated pipette tip device, is illustrated as an openingwith a substantially constant diameter from the top to the bottom of thecentral channel. The channel 19 can align with channel 19 a in thepipette tip of card 16. In the embodiment illustrated in FIG. 1F centralbore 19′ through which the dispenser channel enters and engages thetwo-piece integrated pipette tip device, is illustrated as an opening ingasket 12 with a first diameter that engages an inner surface of thecentral channel 19′a of pipette tip 18 that has a second, largerdiameter. The channels 19, 19 a, 19′ and 19 a′ independently are of anysuitable shape and are cylindrical or frustrum shaped in someembodiments.

In certain embodiments, as illustrated in FIG. 1F, upper surface 20 ofcard 16 can have a substantially flat surface (e.g., no depression inupper surface of card 16), and annular protrusion 14, 14′ of gasket 12can fit within a central bore 19, 19′ in card 16 (e.g., illustrated inFIG. 1F). Central bore 15 of aperture 26, and annular protrusion 14′sometimes are configured to align with, and sealingly engage the openingof central bore 19′ of card 16′. In the embodiment illustrated in FIG.1F, the central bore, through which the dispenser channel enters andengages the two-piece integrated pipette tip device (illustrated by thevertical dashed lines in FIG. 1F), is illustrated as an opening with twodiameters, where the diameter of bore 15 through gasket 12 is less thanthe diameter of bore 19′ through card 16′, and the diameter of opening15 and annular protrusion 14 can fit within opening 19′. In someembodiments, the diameter of the channel can be the same for the gasketpiece and pipette tip-card piece (e.g., as illustrated in FIG. 1E). Insome embodiments, the channel diameter can be different for the gasketpiece and the pipette tip-card piece (e.g., as illustrated in FIG. 1F).In some embodiments, the upper and lower openings of a gasket pieceand/or pipette tip card piece can be (i) connected by tapered or slopedinner pipette tip walls, or (ii) non-tapered or sloped substantiallyvertical walls. In some embodiments, the upper and lower openings of agasket piece and/or pipette tip card piece can be connected by taperedor sloped inner pipette tip walls that are co-extensive withsubstantially vertical dispenser engagement sealing members (e.g.,substantially vertical ribbed or non-ribbed collar; see FIG. 5A fornon-limiting examples of pipette tips with ribbed and non-ribbed sealingmembers). In FIGS. 1E and 1F, the central bore openings are of anysuitable diameter for the gasket-card engagement and engagement of adispensing device.

A gasket can be affixed to a card in a two-piece device in any suitablemanner. A gasket sometimes is affixed by a friction fit, sometimes isaffixed by an adhesive, and sometimes is molded to the card (e.g., in adouble-shot molding process). In some embodiments, two-piece integratedpipette tip devices may be used to handle fluids by: engaging adispensing device; drawing a fluid into pipette tips; emitting the fluidin the pipette tips from the pipette tips. An integrated pipette tipdevice may be ejected from the dispensing device after the fluid isemitted from the pipette tips, in certain embodiments. In someembodiments the pipette tips of an integrated pipette tip deviceoptionally may be rinsed (e.g., at a washing station of a biologicalworkstation configured with a suitable washing platform).

One-Piece Devices and Methods of Use

In some embodiments, an integrated pipette tip device 40 may include acard 42 in connection with a plurality of pipette tips 44, asillustrated in FIG. 2A. Card 42 has a first surface 46 and an opposingsecond surface 48. As described above for two-piece devices, the firstand second surfaces often are substantially planar, and substantiallyparallel to each other. In some embodiments, first (or upper) surface 46may be substantially flat.

One-piece integrated pipette tip device 40 also has symmetricalapertures 52 (illustrated in FIG. 2B) traversing the thickness of card42 and a plurality of pipette tip 44 distal regions can extend from thesecond surface 48 of the card (illustrated in FIG. 2A). In someembodiments, a plurality of pipette tip 44 distal regions can extendfrom a plurality of substantially vertical sealing members that canextend from the second surface 48 of card 42 (illustrated in FIG. 2A).In certain embodiments, apertures 52 in card 42 are coaxially alignedand concentric with distal regions of each pipette tip 44. In someembodiments, a dispenser can engage aperture(s) 52 in a one-pieceintegrated pipette tip device.

One-piece integrated pipette tip device 40, 80 also may include bores54, 92 having an opening located on card 42, 90 at the intersection offour apertures 52, 88, in some embodiments (see FIGS. 2B and 5C). Insome embodiments, the boundaries of bores 54, 82 are delineated by linesor curves (50 in FIG. 2B) connecting four points located between anyfour apertures arranged in a two by two (2×2) array. Where four pointsare drawn on four apertures arranged in a 2×2 array, and the points areconnected, the intersection of the diagonal lines connecting the pointsdefine the center point of the opening for the bore between theapertures in the 2×2 array. This central opening is shown for bore 54 inFIG. 2B and bore 92 in FIG. 5C. In certain embodiments, bores 54, 92extend through a portion of the thickness of, or through the entirethickness of, card 42, as shown in FIGS. 2C and 2D. In some embodimentsthe cross section of bore 54, 92 is substantially square shaped ordiamond shaped. A bore may have any other suitable cross-sectionalshape, such as a circular, oval or other cross-sectional shape.

FIG. 2C illustrates one embodiment of a bore 54 a in which about onethird of the card thickness in the bore is removed and configured toenhance card flexibility of the region that engages a dispenser. FIG. 2Dillustrates an alternate embodiment of bore 54 b in which substantiallygreater than about 90% of the card thickness is removed to enhance cardflexibility (e.g., greater than about 90%, greater than about 91%,greater than about 92%, greater than about 93%, greater than about 94%,greater than about 95%, greater than about 96%, greater than about 97%,greater than about 98%, greater than about 99%, about 100%, orsubstantially all of the card thickness is removed). In certainembodiments, channel 53 may be cylindrical or frustrum shaped.

The lines or curves defining a bore opening (top view) may be of thesame length or of different lengths, in certain embodiments. In someembodiments, the points may be equidistant from each other, with linesor curves (50) of substantially equal lengths or arcs joining thepoints. In certain embodiments, the points may not be equidistant, andare joined by lines or curves (50), where the lines or curves joiningthe points may be substantially different lengths or arcs. In someembodiments, each side of the square or diamond is a curved side (50).Bores 54, 92 can allow for movement of plastic in card 42 when thenozzles of a dispensing device engage the apertures 52, 88 of integratedpipette tip device 40, 80, thereby enhancing flexibility of the devicein the dispenser sealing zone.

As shown in FIG. 2E, in some embodiments, a one-piece integrated card(e.g., 42, 62, 82) may have annular protrusions and/or depressionsextending from first surface 46, 64, surrounding each of the apertures52. FIG. 2E shows an embodiment in which aperture 52 is surrounded byconcentric annular depression 55, which in turn is inset in concentricannular protrusion 56. FIG. 2F shows these features in cross section,and shows channel 53 coextensive with aperture 52. Channel 53 can becylindrical or frustrum shaped in some embodiments.

FIG. 4A to FIG. 4G show cross section views of various sealing memberembodiments, and configurations for receiving sealing members. FIG. 4Ashows a device embodiment that includes an annular depression havingdepressed surface 55, which depression is depressed from the firstsurface of the card. The depression is around, and concentric with,circular aperture 52. Channel 53 and the outer surface 44 of a pipettetip distal region are shown. FIG. 4B shows an embodiment in which anannular depression having surface 55 is depressed from surface 56 of aprotrusion extending from the first surface of the card. FIG. 4C andFIG. 4D show embodiments in which sealing member 59 a is seated in thedepression having surface 55, where the top surface of the sealingmember is flush or substantially flush with the first surface of thecard or surface 56 of the protrusion. FIG. 4E and FIG. 4F showembodiments in which sealing member 59 b is seated in the depressionhaving surface 55, where the top surface of the sealing member is proudof or raised above the first surface of the card or surface 56 of theprotrusion. FIG. 4G shows an embodiment in which sealing member 59 c isdeposited on a substantially flat first surface of the card, which cardsurface includes no depression or protrusion around the aperture. FIG.4H shows a top view of certain sealing member embodiments shown in FIG.4A to FIG. 4G. In embodiments shown in FIG. 4A to FIG. 4H, the sealingmember often is substantially resilient and often comprises asubstantially flexible material (e.g., an elastomer, examples of whichare described herein). The sealing member in such embodiments often ismore resilient than the pipette tips and card of the device. The sealingmember sometimes is a member separate from the device that is pressedinto or onto the device, sometimes is retained by a friction fit in thedevice, and sometimes is retained by an adhesive. The sealing membersometimes is molded onto or into the device, sometimes by a double shotmolding process, for example. The sealing member in such embodiments cansealingly engage and disengage a dispenser and promote efficientengagement and disengagement of the integrated pipette tip device anddispenser.

As shown in FIG. 5A, one-piece devices sometimes include a sealingmember 84 or 85 (also referred to herein as a collar), having an outerwall that extends in a substantially vertical orientation from the cardbottom surface 81. Sometimes the collar is a sealing member 84 havingribs 87 and sometimes the collar is a non-ribbed sealing member 85. Adevice sometimes includes collars having no ribs, ribs, no depressions,depressions, the like, or a combination thereof. The frustum shapedpipette tip distal portion 86 is co-extensive with a sealing member(e.g., substantially vertically ribbed sealing member 84 or non-ribbedproximal collar sealing member 85). Sealing members (e.g., ribbeddispenser engagement zones, non-ribbed dispenser engagement zones) canbe of any configuration suitable for use in devices described herein. Insome embodiments, ribbed sealing member walls have an outer surface onwhich ribs of a first thickness are disposed around the circumference ofthe walls. The ribs are regularly spaced around the circumference insome embodiments, and sometimes are irregularly spaced around thecircumference. In some embodiments, the ribs are uniform (e.g.,substantially similar thicknesses, substantially similar widths,substantially similar shapes, substantially similar tapers, the like orcombinations thereof), and in certain embodiments, the ribs arenon-uniform (e.g., different thicknesses, different widths, differentshapes, different tapers, the like or combinations thereof).Non-limiting examples of ribbed sealing members are known in the art(e.g., U.S. patent application 20110183433, incorporated by referenceherein in its entirety).

FIG. 5B shows a bottom view of a one-piece integrated pipette tip deviceshowing ribbed collars 84 and non-ribbed collars 85. FIG. 5C is a bottomview of a one-piece integrated pipette tip device having a bores inwhich substantially all of the card thickness is removed in the bore.The bores in FIG. 5C may provide flexibility during tip engagement to,and dispensing from, a dispenser. In some embodiments, reinforcing ribsdescribed below can be used in conjunction with integrated pipette tipdevice 40, 80 (e.g., FIG. 5D, FIG. 5E).

FIG. 6A shows embodiments in which a device comprises a plurality ofsealing members 141 and/or 142, which sealing members can includesealing member ribs and/or depressions. A sealing member sometimesincludes a flange 135 and sometimes includes no flange. Sealing memberribs or depressions 140 sometimes extend to flange 135 when present andform a rib/depression-flange interface 145. In embodiments where aflange is not present, sealing member ribs or depressions 143 canterminate at a point 144 along the length of the sealing member, andsometimes can terminate at the top perimeter of the sealing zone. Shownalso in FIG. 6A is second surface 130 of the card and an outer surface125 of pipette tips. FIG. 6B shows embodiments in which a devicecomprises a plurality of sealing members 225 that include a flange 235or no flange, include ribs and/or depressions 240, rib or depressiontermini 245, sealing member top perimeter 230, second surface 204,pipette tip outer surface 210. Also shown in FIG. 6B is an axisextending through the pipette tip proximal region (e.g., around the topperimeter of the sealing member or the first surface of the card) anddistal region (e.g., pipette tip bottom), and oriented at the center ofthe aperture, sealing member and pipette tip diameters. FIG. 6B alsoshows pipette tip stabilizing rib embodiments 220 and 215, which connectto the pipette tip outer surface and to the second surface of the card.FIG. 6C shows pipette tip stabilizing rib embodiments 250, 260 and 270in connection with two pipette tips and the second surface of the card.

In some embodiments, integrated pipette tip device 40, 80 may be used tohandle fluids by: engaging a dispensing device; drawing a fluid intopipette tips; and emitting the fluid in the pipette tips from thepipette tips. The integrated pipette tip device may be ejected from thedispensing device after the fluid is emitted from the pipette tips, incertain embodiments. In some embodiments the pipette tips of anintegrated pipette tip device optionally may be rinsed at the washingstation of a biological workstation configured with a suitable washingplatform.

One-Piece Integrated Pipette Tip Device with Reinforcing Ribs

In some embodiments, an integrated pipette tip device 60 may include acard 62 in connection with a plurality of pipette tips 68 and two ormore ribs 70, 72 in connection with each pipette tip, as illustrated inFIG. 3A. Features described for cards 16, 42, and 80 can be incorporatedinto card 62 to generate one-piece integrated pipette tip devices withreinforcing ribs that include additional features found in other deviceembodiments described herein. Ribs 70 and 72 may co-extend from secondsurface 66, 81 and can extend from in the range of about one quarter 70to about three quarters 72 of the length of distal portion of pipettetips 68, 86, in some embodiments. The length of the ribs can be of anydimension that does not interfere with subsequent liquid dispensingoperations and provides adequate lateral support to maintainconcentricity of upper and lower pipette tip openings. FIG. 5D shows ribembodiments 101 and 102 with cards having ribbed collar regions. Whereribs connect only to pipette tip surface 68 and bottom card surface 66(e.g., rib 70), and do not attach to surfaces of two pipette tips (e.g.,rib 74), each pipette tip often is in association with two or more suchribs. A card may include only one rib configuration (e.g., only rib 101or rib 70 and not rib 102 or rib 72), and sometimes a card includes twoor more rib configurations (e.g., ribs 70 and 72 in the same card).

In some embodiments, an alternative configuration of reinforcing ribsmay be used, as illustrated in FIGS. 3B and 5E. Ribs 74, 76, and 78interconnect two adjacent pipette tips 68, 86. Each pipette tip 68, 86is still in connection with two or more ribs, although each rib connectstwo pipette tips, instead of two ribs being connected to one pipettetip, as illustrated in FIG. 3A. Ribs 74, 76 and 78 may be co-extrudedfrom second surface 66, 81, and can extend from in the range of aboutone quarter 74 to about three quarters 78 of the length of distalportion of pipette tips 68, 86. Rib 76, as illustrated in FIG. 3B, isapproximately one half the length of pipette tip 68. In someembodiments, a combination of ribs illustrated in FIGS. 3A, 5D, 3B and5E may be used. Integrated pipette tip device 60, 80 may be configuredto have ribs (70, 72, in FIG. 3A and the equivalent ribs illustrated inFIG. 5D) along the length of each pipette tip 68, 86 and also havehorizontally interconnected ribs (74, 76 and 78, in FIG. 3B) betweenadjacent pipette tips. In some embodiments the two or more ribs inconnection with each pipette tip can be in contact with an adjacentpipette tip distal region. FIG. 5E shows rib embodiments 110, 112 and114 with cards having ribbed collar regions. Where ribs attach tosurfaces of two pipette tips (e.g., rib 74), each pipette tip often isin association with two or more such ribs. A card may include only onerib configuration (e.g., only rib 101 or rib 70 and not rib 102 or rib72), and sometimes a card includes two or more rib configurations (e.g.,ribs 70 and 72 in the same card). In certain embodiments, a cardincludes only ribs of type 70 and/or 72, and not type 74, 76 and/or 78,a card includes only ribs of type 74, 76 and/or 78 and not ribs of type70 and/or 72, or a card includes ribs of type 74, 76 and/or 78 and ribsof type 70 and/or 72.

Card 62 also has a first surface 64 and an opposing second surface 66.As described above, the first and second surfaces are oftensubstantially planar in shape, and substantially parallel to each other.In some embodiments, first (or upper) surface 64 may be substantiallyflat. One-piece integrated pipette tip device 60 also has symmetricalapertures 82 (illustrated in FIG. 3C) traversing the thickness of card62 and a plurality of pipette tip 68 distal regions can extend from thesecond surface 66 of the card (illustrated in FIGS. 3A and 3B). In someembodiments, apertures 82 in card 62 are coaxially aligned andconcentric with distal regions of each pipette tip 68. One-pieceintegrated pipette tip device 60 can also be referred to as a “one-pieceribbed device.” One-piece ribbed devices sometimes optionally includesubstantially vertical sealing members that extend from the secondsurface of card 62 and the distal region of each pipette tip 68 extendsfrom the sealing members. In embodiments including sealing members, thesealing members sometimes are ribbed sealing members and sometimes arenon-ribbed sealing members. In certain embodiments, reinforcing ribs maybe used to interconnect two adjacent pipette tips. The ribs can provideadditional rigidity to decrease lateral displacement, or deviations inconcentricity (e.g., bending or curving of thin walled pipette tips)that can sometimes occur with smaller pipette tips designed fordispensing devices having 96 or more nozzles. In some embodiments,annular protrusion 32 may be optionally included on the upper surface ofintegrated card 62, around apertures 82, which can aid sealingengagement of dispenser channels, and decrease the incidence of samplecross contamination, in some embodiments. In some embodiments annularprotrusion 32 is made of the same material as the rest of the card, andin certain embodiments annular protrusion 32 is made of a differentmaterial from the rest of the card. In some embodiments, annularprotrusion 32 is made from a polymer, and in certain embodiments annularprotrusion is made from a thermoplastic elastomer. Non-limiting examplesof thermoplastic elastomers suitable for use in annular protrusions aredescribed herein.

In some embodiments, integrated pipette tip device 60 may be used tohandle fluids by: engaging a dispensing device; drawing a fluid intopipette tips; and emitting the fluid in the pipette tips from thepipette tips. The integrated pipette tip device may be ejected from thedispensing device after the fluid is emitted from the pipette tips, incertain embodiments. In some embodiments the pipette tips of anintegrated pipette tip device optionally may be rinsed at the washingstation of a biological workstation configured with a suitable washingplatform.

Although multiple configurations are shown in certain figures herein, itis understood that one device my include only one type of member shownor may include a combination of members. For example, a device mayinclude only one type of pipette tip stabilizing rib embodiment shown inFIG. 6B or FIG. 6C, or a combination of such embodiments. A device alsomay include only one type of sealing member (e.g., a sealing memberhaving a flange or a sealing member not having a flange (shown in FIG.6A)), or a combination of sealing member embodiments. In anotherexample, a device may include only one type of configuration around anaperture, such as no depression, no protrusion, a depression, aprotrusion, no sealing member, a sealing member, or may include acombination of such configurations (e.g., FIG. 4H).

Features Common to One-Piece and Two-Piece Devices

The pipette tip portion of an integrated pipette tip device can be ofany geometry useful for dispensing fluids in combination with adispensing device. The pipette tip portion of an integrated pipette tipdevice can be of any volume useful for dispensing fluids in combinationwith a dispensing device. The pipette tip portions extending below thelower surface of the card can be configured in sizes that hold from 0 to10 microliters, 0 to 20 microliters, 1 to 100 microliters, 1 to 200microliters and from 1 to 1000 microliters, for example. The externalappearance of pipette tips may differ, and certain pipette tips can havea continuous tapered wall forming a central channel or tube that isroughly circular in horizontal cross section, in some embodiments. Apipette tip can have any cross-sectional geometry that results in a tipthat (i) provides suitable flow characteristics, and (ii) can be fittedto a dispenser (e.g., pipette), for example.

Pipette tips sometimes have a cylindrical region which extends from thesecond surface of a card that acts as a sealing member for an inserteddispensing tool or apparatus. A sealing member sometimes is in contactwith the first or second surface of a card, and sometimes anotherportion of a pipette tip, such as a portion of a distal region forexample, is in contact with the first or second surface of a card. Aterminal portion of a sealing member can be located about 0.126 inchesto about 2.00 inches from the first or second surface of a card. Asealing member sometimes has a thickness of about 0.005 inches to about0.015 inches. A top surface of a card can intersect each pipette tip ina pipette tip array at a cross sectional plane of the pipette tip, wherethe cross sectional plane is located at a point on a longitudinal axisintersecting the distal terminus and proximal terminus of the pipettetip. The point on the longitudinal axis sometimes is a distance from thedistal terminus of the pipette tip equal to, or about equal to, 30% to95% of the total length of the pipette tip from the distal terminus tothe proximal terminus (e.g., a distance of about 35%, 40%, 45%, 50%,55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% the total length of the pipettetip). The distal portion or tapered portion of the pipette tip sometimesis co-extensive with the cylindrical sealing member which extends fromthe second surface of the pipette card. In some embodiments the sealingmember is ribbed and in certain embodiments the sealing member is anon-ribbed proximal collar.

Pipette tips sometimes taper from the widest point at the top-mostportion of the pipette tip (pipette proximal end or end that engages adispenser), to a narrow opening at the bottom most portion of thepipette tip (pipette distal end that extends below the card or end usedto acquire or dispel fluid). In certain embodiments, a pipette tip wallincludes two or more taper angles. The inner surface of the pipette tipsometimes forms a tapered continuous wall, in some embodiments, and incertain embodiments, the external wall may assume an appearance rangingfrom a continuous taper to a stepped taper or a combination of smoothtaper with external protrusions. The bore of the top-most portion of thecentral channel or tube generally is wide enough to accept a particulardispenser apparatus (e.g., nozzle, barrel).

The wall of the distal region of a pipette tip of Integrated pipette tipdevices (e.g., the portion extending below the card or snap plate),sometimes is continuously tapered from the wider portion, which is ineffective connection with the proximal section, to a narrower terminus.The wall of the distal region, in some embodiments, forms a steppedtapered surface. The angle of each taper in a distal region is betweenabout zero degrees to about thirty degrees from the central longitudinalvertical axis of the pipette tip (e.g., about 0, 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29 or 30 degrees), in certain embodiments. In some embodiments,the wall of the distal region forms stepped vertical sections. The wallthickness of a distal region may be constant along the length of thesection, or may vary with the length of the section (e.g., the wall ofthe distal region closer to the proximal section of the pipette tip maybe thicker or thinner than the wall closer to the distal regionterminus; the thickness may continuously thicken of thin over the lengthof the wall). The distal region of a pipette tip generally terminates inan aperture through which fluid passes into or out of the distalportion. A distal region of a pipette tip may contain a filter, insertor other material.

The wall of the proximal section of devices described herein (e.g.,portion contained within the thickness of the card, or projecting abovethe upper surface of the card or projecting below the lower surface ofthe card) sometimes is continuously tapered from the top portion, to anarrower terminus, sometimes is stepped from a region of constantcircumference to a continuously tapered region from an upper portion toa narrower terminus, and sometimes is not tapered and/or not stepped. Insome embodiments the region of constant circumference is a ribbedsealing member. In certain embodiments, the contribution of the constantcircumference portion to the total length of the pipette tip extendingbelow the second surface of the card is about ⅓ of the total length ofthe pipette tip.

The top portion generally is open and often is shaped to receive apipette tip engagement portion of a dispensing device. The wall of aproximal section, in some embodiments, forms a stepped tapered surface.The angle of each taper in the proximal section is between about zerodegrees to about thirty degrees from the central longitudinal verticalaxis of the pipette tip (e.g., about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29 or 30 degrees), in certain embodiments. The wall thickness of aproximal section may be constant over the length of the section, or mayvary with the length of the proximal section (e.g., the wall of theproximal section closer to the distal region of the pipette tip may bethicker or thinner than the wall closer to the top of the proximalsection; the thickness may continuously thicken or thin over the lengthof the wall). A proximal section of a pipette tip may contain a filter,insert or other material. The interior bore of a pipette tip, in thedistal region or proximal region, or distal region and proximal region,sometimes is substantially cylindrical and often is substantiallyfrustrum shaped (e.g., bore 19 a or 19 a′ in FIGS. 1E and 1F, and bore53 in FIGS. 2C, 2D, 2F, 4A, 4B, 4C, 4D, 4E, 4F and 4G).

Integrated pipette tip devices described herein often are configured foruse with standard pipette tip storage units. The cards can be configuredto have substantially the same planar shape and dimensions ascommercially available pipette tip storage boxes or storage units. Acard often is substantially rectangular in shape, where the length ofone set of parallel sides can be in the range of about 120 to about 140millimeters, and more specifically between about 125 to about 135millimeters, in some embodiments (e.g., about 120 millimeters, about 125millimeters, about 126 millimeters, about 127 millimeters, about 128millimeters, about 129 millimeters, about 130 millimeters, about 131millimeters, about 132 millimeters, about 133 millimeters, about 134millimeters, about 135 millimeters, or about 140 millimeters). Thesecond set of parallel sides can be in the range of about 70 to about100, and more specifically about 80 to about 90 millimeters, in someembodiments (e.g., about 70 millimeters, about 75 millimeters, 80millimeters, about 81 millimeters, about 82 millimeters, about 83millimeters, about 84 millimeters, about 85 millimeters, about 86millimeters, about 87 millimeters, about 88 millimeters, about 89millimeters, about 90 millimeters, about 95 millimeters, or about 100millimeters). The integrated cards can range in thickness from about 0.5to about 5 milliliters, in certain embodiments (e.g., about 0.5millimeters, about 0.6 millimeters, about 0.7 millimeters, about 0.8millimeters, about 0.9 millimeters, about 1.0 millimeter, about 1.1millimeters, about 1.2 millimeters, about 1.3 millimeters, about 1.4millimeters, about 1.5 millimeters, about 1.6 millimeters, about 1.7millimeters, about 1.8 millimeters, about 1.9 millimeters, about 2.0millimeters, about 2.1 millimeters, about 2.2 millimeters, about 2.3millimeters, about 2.4 millimeters, about 2.5 millimeters, about 2.6millimeters, about 2.7 millimeters, about 2.8 millimeters, about 2.9millimeters, about 3.0 millimeters, about 3.1 millimeters, about 3.2millimeters, about 3.3 millimeters, about 3.4 millimeters, about 3.5millimeters, about 3.6 millimeters, about 3.7 millimeters, about 3.8millimeters, about 3.9 millimeters, about 4.0 millimeters, about 4.1millimeters, about 4.2 millimeters, about 4.3 millimeters, about 4.4millimeters, about 4.5 millimeters, about 4.6 millimeters, about 4.7millimeters, about 4.8 millimeters, about 4.9 millimeters, or about 5.0millimeters). The thickness of the cards is from about 20% to about 80%of the overall height of the card.

Pipette tips of the one-piece and two-piece integrated cards often arearranged in substantially planar arrays. The term “array” as used hereinrefers to an arrangement of pipette tips across a two-dimensionalsurface. An array may be of any convenient general shape (e.g.,circular, oval, square, rectangular). An array may be referred to as an“X by Y array” for square or rectangular arrays, where the arrayincludes X number of pipette tips in one dimension and Y number ofpipette tips in a perpendicular dimension. For example, a “12 by 8array” includes twelve pipette tips in one dimension and eight pipettetips in a perpendicular dimension, where the array includes a total ofninety-six (96) pipette tips. An array may be symmetrical (e.g., a 16 by16 array) or non-symmetrical (e.g., an 8 by 16 array). An array mayinclude any convenient number of pipette tips in any suitablearrangement. For example, X or Y independently can be 1 to 64 (e.g., 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24,26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60,62), and sometimes independently can be 6, 12, 16, 24, 32, 48 or 64. Insome embodiments, X multiplied by Y yields 96, 384 or 1536, andsometimes arrays provided in a tray total to 96, 384 or 1536 pipettetips. Non-limiting examples of array configurations with 96, 384 or 1536pipette tips are; a 12 by 8 or 6 by 16 array for configurations of 96tips, a 24 by 16, 12 by 32 or 8 by 48 array for configurations of 384tips, and a 24 by 64 or 48 by 32 array for configurations of 1536 tips.In some embodiments, the one and two-piece integrated pipette tipdevices (20, 40, and 60) include 384 pipette tips. In some embodiments,the one and two-piece integrated pipette tip devices (20, 40, and 60)include 1536 pipette tips.

In some embodiments, one and two-piece integrated pipette tip devices(20, 40, and 60) can be configured as sub-regions in a rack, or multipleregions may be provided in a rack. For example, a rack may contain twoor more integrated pipette tip devices or regions, in some embodiments(e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23 or 24 separate devices or regions in one rack). Incertain embodiments, an edge of each separate device or region isconnected to an edge of another separate region. In certain embodiments,an integrated pipette tip device may be separated into two or moresub-regions (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23 or 24 sub-regions in one rack). A sub-regionin some embodiments is a quadrant. A card including 384 or 1536 pipettetips, can be divided into four sub-regions, each containing 96, or 384pipette tips, respectively. The demarcation between the sub-regions canbe an area of scoring or a frangible area to allow the card to be usedin a modular fashion. Individual sub-regions may be separated (e.g.,completely separate, induced separation) to allow a subset of thepipette tips to be used, as desired by the operator. In someembodiments, for a rack providing an integrated pipette tip devicehaving sub-regions that can be separated, the attractive force (e.g.,frictional force) between the pipette tips and nozzles of a dispenserfor one sub-region is greater than the attractive force betweensub-regions, which allows the dispensing device to pull each sub-regionfrom the rack independent of other sub-regions. In certain embodiments,for a rack providing multiple integrated pipette tip devices, theattractive force between the pipette tips and nozzles of a dispenser foreach region is greater than the attractive force between regions, whichallows the dispensing device to pull each region from the rackindependent of other regions.

In some embodiments, the card portion of one and two-piece integratedpipette tip devices (20, 40, 60 and 80) can be constructed from a firstmaterial and the gasket in two-piece devices may be constructed from asecond material relatively more resilient than the first material. Insome embodiments the first material may be a moldable plastic. In someembodiments, the annular protrusion protruding above the first surfaceof one and two-piece integrated pipette tip devices is made from thesame material as the card, and in certain embodiments, the annularprotrusion protruding above the first surface of one or two-pieceintegrated pipette tip devices may be constructed from a second materialrelatively more resilient than the first material (e.g., the material ofthe card). Non-limiting examples of moldable plastics include,polypropylene (PP), polyethylene (PE), high-density polyethylene,low-density polyethylene, polyethylene teraphthalate (PET), polyvinylchloride (PVC), polytetrafluoroethylene (PTFE), polystyrene (PS),high-density polystyrene, acrylnitrile butadiene styrene copolymers,plastics with higher flow and lower viscosity or a combination of two ormore of the foregoing.

Non-limiting examples of plastics with higher flow and lower viscosityinclude, any suitable material having a hardness characterized by one ormore of the following properties, in certain embodiments: a melt flowrate (230 degrees Celsius at 2.16 kg) of about 30 to about 75 grams per10 minutes using an ASTM D 1238 test method; a tensile strength at yieldof about 3900 to about 5000 pounds per square inch using an ASTM D 638test method; a tensile elongation at yield of about 7 to about 14% usingan ASTM D 638 test method; a flexural modulus at 1% sectant of about110,000 to about 240,000 pounds per square inch using an ASTM D 790 testmethod; a notched Izod impact strength (23 degrees Celsius) of about 0.4to about 4.0 foot pounds per inch using an ASTM D 256 test method;and/or a heat deflection temperature (at 0.455 MPa) of about 150 degreesto about 500 degrees Fahrenheit using an ASTM D 648 test method. Amaterial used to construct the pipette tips and card include moldablematerials in some embodiments. Non-limiting examples of materials thatcan be used to manufacture the pipette tips and cards includepolypropylene, polystyrene, polyethylene, polycarbonate, and the like,and mixtures thereof. Materials suitable for use in embodimentsdescribed herein, and methods for manufacture using those materials havebeen described in published United States Patent Application No.20100218622, filed on Jan. 11, 2010, and entitled “FLEXIBLE PIPETTETIPS”, the entirety of which is hereby incorporated by reference herein.

In some embodiments a substantially resilient material comprising amoldable thermoplastic elastomer (TPE) is used to manufacture the gasketportion of a two-piece integrated pipette tip device and/or a sealingmember. Non-limiting examples of TPE's include, styrenic blockcopolymers, polyolefin blends, elastomeric alloys, thermoplasticpolyurethanes, thermoplastic copolyester and thermoplastic polyamides.Examples of TPE products from the block copolymers group are STYROFLEX(BASF), KRATON (Shell Chemicals), PELLETHANE (Dow chemical), PEBAX,ARNITEL (DSM), HYTREL (Du Pont) and more. Examples of commerciallyavailable elastomeric alloys include SANTOPRENE (in-situ cross linkedpolypropylene and EPDM rubber; Monsanto), GEOLAST (Monsanto) and ALCRYN(Du Pont). Further examples of the materials that can be used toconstruct the annular protrusion include, without limitation,thermoplastic vulcanizates (TPV; SANTOPRENE TPV), thermoplasticpolyurethane (TPU), thermoplastic olefins (TPO), polysulfide rubber,ethylene propylene rubber (e.g., EPM, a copolymer of ethylene andpropylene), ethylene propylene diene rubber (e.g., EPDM, a terpolymer ofethylene, propylene and a diene-component), epichlorohydrin rubber(ECO), polyacrylic rubber (ACM, ABR), silicone rubber (SI, Q, VMQ),fluorosilicone Rubber (FVMQ), fluoroelastomers (e.g., FKM, and FEPM,VITON, TECNOFLON, FLUOREL, AFLAS and DAI-EL), perfluoroelastomers (e.g.,FFKM, TECNOFLON PFR, KALREZ, CHEMRAZ, PERLAST), polyether block amides(PEBA), chlorosulfonated polyethylene (CSM, e.g., HYPALON),ethylene-vinyl acetate (EVA), synthetic polyisoprene (IR), butyl rubber(copolymer of isobutylene and isoprene, IIR), halogenated butyl rubbers(chloro butyl rubber: CIIR; bromo butyl rubber: BIIR), polybutadiene(BR), styrene-butadiene rubber (copolymer of polystyrene andpolybutadiene, SBR), nitrile rubber (copolymer of polybutadiene andacrylonitrile, NBR; Buna N rubbers), hydrogenated nitrile rubbers (HNBR,THERBAN and ZETPOL), chloroprene rubber (CR, polychloroprene, NEOPRENE,BAYPREN) and the like.

Substantially resilient sealing members (e.g., including an elastomericmaterial (e.g., TPE)) can be associated with a device by any suitablemethod. In some embodiments, a sealing member is manufactured as aseparate element and is pressed onto a device. Such a separate elementcan be affixed to the device by friction and optionally is affixed tothe device by a suitable adhesive. In certain embodiments, a sealingmember is molded onto a device. A sealing member can be molded onto adevice as part of a double-shot molding process, where the card andpipette tips are molded in one shot and the sealing members are moldedin another shot, for example.

In some embodiments anti-microbial agents or substances may be added tothe moldable plastic during the manufacture process. In someembodiments, the anti-microbial agent or substance can be ananti-microbial metal. The addition of anti-microbial agents may beuseful in (i) decreasing the amount of microbes present in or on adevice, (ii) decreasing the probability that microbes reside in or on adevice, and/or (iii) decreasing the probability that microbes form abiofilm in or on a device, for example. Non-limiting examples of metalswith anti-microbial properties are silver, gold, platinum, palladium,copper, iridium (i.e. the noble metals), tin, antimony, bismuth, zinccadmium, chromium, and thallium. The afore-mentioned metal ions arebelieved to exert their effects by disrupting respiration and electrontransport systems upon absorption into bacterial or fungal cells. Acommercially accessible form of silver that can be utilized in devicesdescribed herein is SMARTSILVER NovaResin. SMARTSILVER NovaResin is abrand of antimicrobial master batch additives designed for use in a widerange of polymer application. Billions of silver nanoparticles caneasily be impregnated into PET, PP, PE and nylon using standardextrusion or injection molding equipment. SMARTSILVER NovaResinadditives may be delivered as concentrated silver-containing masterbatch pellets to facilitate handling and processing. NovaResin isdesigned to provide optimum productivity in a wide range of processes,including fiber extrusion, injection molding, film extrusion andfoaming.

Further non-limiting examples of anti-microbial substances or agentsinclude, without limitation, inorganic particles such as barium sulfate,calcium sulfate, strontium sulfate, titanium oxide, aluminum oxide,silicon oxide, zeolites, mica, talcum, and kaolin. Methods ofmanufacture of anti-microbial containing plastics, and amounts ofanti-microbial substances used in manufacture of anti-microbialcontaining plastics have been described in published United StatesPatent Application No. 20110259443, filed on Dec. 16, 2010, and entitled“ANTIMICIROBIAL FLUID HANDLING DEVICES AND METHODS OF MANUFACTURE”, theentirety of which is hereby incorporated herein by reference.

In certain embodiments anti-static agents can be incorporated into themoldable plastic during the manufacture process. In certain embodiments,an anti-static agent can be an electrically conductive member. Incertain embodiments, an integrated pipette tip device is in contact withan electrically conductive member, or portions thereof, which is incommunication with the interior or exterior of a pipette tip storageunit. This contact may allow the static charge from the pipette tips tobe discharged.

An electrically conducting member may include any type of electricallyconductive material, such as a conductive metal for example.Non-limiting examples of electrically conductive metals include,platinum (Pt), palladium (Pd), copper (Cu), nickel (Ni), silver (Ag) andgold (Au). The metals may be in any form in or on the conductive member,for example, such as metal flakes, metal powder, metal strands orcoating of metal. An electrically conductive member, or portionsthereof, may include a metal, polymeric material, foam, film, sheet,foil, salt or combinations thereof. In some embodiments, a conductivemetal foil may be utilized for one or more components of a pipette tiptray (e.g., copper-aluminum foil; label adhered to an electricallyconductive tab on exterior of a pipette tip tray component).

The electrically conductive materials, or portions thereof, may be anymaterial that can contain movable electric charges, for example such ascarbon. In some embodiments, the electrically conductive member includesabout 5% to about 40% or more carbon by weight (e.g., 7-10%, 9-12%11-14%, 13-16%, 15-18%, 17-20%, 19-22%, 21-24%, 23-26%, 25-28%, 27-30%,29-32%, 32-34%, 33-36%, or 35-38% carbon by weight). In certainembodiments, an electrically conductive film is utilized that includescarbon (e.g., commercially available from Gemini Plastic Enterprises,Inc., California). An electrically conductive film in some embodimentscontains ethylene vinyl acetate (EVA), which can impart a supple qualityto the film (e.g., about 5% to about 25% EVA by weight; about 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24% EVA).Methods of manufacture of anti-static member containing plastics, andamounts of anti-static members used in manufacture of anti-static membercontaining plastics have been described in published United StatesPatent Application No. 20100221151, filed on Jan. 22, 2010, and entitled“ANTI-STATIC PIPETTE TIP TRAYS”, and is hereby incorporated herein, inits entirety.

In some embodiments, the proximal region, or a portion thereof, ofpipette tips in an integrated pipette tip device does not project beyondthe upper surface of the card with which the pipette tips are integrated(e.g., aperture openings of the pipette tips are co-extensive with theupper surface of the card in one-piece devices). In certain embodiments,apertures of each pipette tip member in an integrated pipette tip deviceare surrounded by material that is about 2 millimeters thick or less(e.g., in a one-piece device). In particular embodiments, the thicknessof pipette tip elements and/or the card element in a device is greaterthan about 0.1 millimeter. In certain embodiments, a device does notinclude, and is not used in conjunction with, a flexible component(e.g., planar component) that covers, and/or seals, an opening of apipette tip proximal region.

In some embodiments, integrated pipette tip devices that are used topresent 96, 384 or 1536 pipette tips in a rack can deliver a volume ofdouble distilled water with a CV of 10% or less, when the pipettor isset at a low or minimum volume. In certain embodiments, integratedpipette tip devices that are used to present 96, 384 or 1536 pipettetips in a rack can deliver volume of double distilled water with a CV of5% or less, when the pipettor is set at a high or maximum volume. Theprecision and accuracy measurements of the pipette tips is dependent onthe condition and calibration of the pipettor being tested with the tipsdescribed herein. In general, accuracy and CV values for devicesdescribed herein can range between 1% and 10% depending on the volume atwhich the pipettor is tested, and the condition and calibration of thepipettor.

Pipette tip “precision” refers to the ability of a plurality of pipettetips to deliver about the same volume of fluid, with a relatively smallstandard deviation, for a given dispenser (e.g., pipette tips stated todeliver 200 microliters of fluid consistently deliver about 197microliters of fluid). Pipette tip “accuracy” refers to the ability of aplurality of pipette tips to deliver a particular volume of fluid (e.g.,pipette tips stated to deliver 200 microliters of fluid deliver, inpractice, about 200 microliters of fluid). One measure of pipette tipprecision is a calculated percent “coefficient of variation,” which alsois referred to herein as “CV” and discussed in greater detail hereafter.

Coefficient of variation (CV) can be calculated for a pipette tip lot ina variety of manners. In general, percent CV equals (a) the quotient of(i) standard deviation in volume dispensed from the pipette tips,divided by (ii) the average volume dispensed from the pipette tips, (b)multiplied by 100. A CV value often is calculated for a particular lotof pipette tips. One of many protocols can be selected for collectingpipette tips in the lot to calculate a CV value. Random pipette tips maybe selected from a lot after a manufacturing run is completed in someembodiments, and in certain embodiments, pipette tips are collected atdifferent time points during the manufacturing run of the lot (e.g.,pipette tips are collected at time points during the manufacture run atregular intervals).

In certain embodiments pertaining to CV measurements, water is dispensedfrom pipette tips of a particular lot using one dispensing device, andvolume of each dispensed amount is weighed. The average and standarddeviation of all weighed aliquots of water then can be calculated insuch embodiments.

In some embodiments pertaining to CV measurements, liquid containing adye is dispensed from each pipette tip into a well of a tray having anarray of wells. The average volume can be determined from the weight ofthe plate containing the dispensed liquid less the weight of the platebefore liquid was dispensed. The standard deviation in volume dispensedinto each well can be determined by optically determining the volume ineach well by the amount of dye in each well (e.g., using a light,fluorescence, luminescence or absorbance detector in a plate reader).

EXAMPLES

The example set forth below illustrates, and does not limit, thetechnology.

Example 1 Examples of Embodiments

Described hereafter are non-limiting examples of certain embodiments.

A1. A two-piece integrated pipette tip device, including a card inconnection with a plurality of integrated pipette tips and a gasket insealing connection with a first surface of the card,

which card and pipette tips are constructed from a first material andthe gasket is constructed from a second material relatively moreresilient than the first material;

each of which pipette tips includes a distal region and each pipette tipextends from a second surface of the card opposite the first surface;

which gasket includes a surface in connection with the first surface ofthe card, which surface of the gasket covers about 80% or more of thefirst surface of the card;

which card includes card apertures defining channels that traverse thethickness of the card, each of which card apertures is concentric withone pipette tip; and

which gasket includes gasket apertures that traverse the thickness ofthe card, each of which gasket apertures is concentric with one cardaperture.

A2. The device of embodiment A1, wherein the gasket includes annulargasket protrusions surrounding the gasket apertures.

A3. The device of embodiment A2, wherein each gasket protrusions isconfigured to sealingly engage an inner surface of one card aperture.

A4. The device of embodiment A2, wherein the card includes annular carddepressions surrounding the card apertures, which card depressions areconcentric with the card apertures and each of which card depressions isconfigured to sealingly engage with one gasket protrusion.A5. The device of embodiment A1, wherein the card includes annular cardprotrusions extending from the first surface, which card protrusionssurround the card apertures and are concentric with the card apertures.A6. The device of embodiment A5, wherein each of the card protrusions isconfigured to sealingly engage with an inner surface of one gasketaperture.A7. The device of embodiment A5, wherein the gasket includes annulargasket depressions surrounding the gasket apertures, which gasketdepressions are concentric with the gasket apertures and each of whichgasket depressions is configured to sealingly engage with one cardprotrusion.A8. The device of any one of embodiments A1 to A7, wherein the surfaceof the gasket in connection with the first surface of the card coversabout 90% or more of the first surface of the card.A9. The device of embodiment A6, wherein the surface of the gasket inconnection with the first surface of the card covers about 95% or moreof the first surface of the card.A10. The device of embodiment A9, wherein the surface of the gasket inconnection with the first surface of the card covers about 100% or moreof the first surface of the card.A11. The device of any one of embodiments A1 to A10, wherein the firstmaterial is a moldable plastic.A12. The device of embodiment A11, wherein the plastic includes one ormore of polypropylene (PP), polyethylene (PE), high-densitypolyethylene, low-density polyethylene, polyethylene teraphthalate(PET), polyvinyl chloride (PVC), polyethylenefluoroethylene (PEFE),polystyrene (PS), high-density polystyrene, acrylnitrile butadienestyrene copolymers, or a combination of two or more of the foregoing.A13. The device of embodiment A12, wherein the plastic includes PE.A14. The device of any one of embodiments A1 to A13, wherein the secondmaterial includes a moldable thermoplastic elastomer.A15. The device of any one of embodiments A1 to A14, wherein the deviceincludes 384 pipette tips.A16. The device of any one of embodiments A1 to A14, wherein the deviceincludes 1536 pipette tips.A17. The device of any one of embodiments A1 to A16, wherein the gasketis substantially flat.A18. The device of any one of embodiments A1 to A17, wherein the distalregion is in connection with the second surface of the card.A19. The device of any one of embodiments A1 to A18, further including aplurality of pipette tip support ribs, each of which pipette tip supportribs is in connection with a pipette tip and the second surface of thecard.A20. The device of embodiment A19, wherein each pipette tip support ribis in contact with the distal region of a pipette tip.A21. The device of embodiment A19 or A20, wherein each pipette tipsupport rib is in contact with two pipette tips.A22. The device of embodiment A19 or A20, wherein each pipette tipsupport rib is in contact with one pipette tip and no other pipette tip.B1. A method for dispensing a fluid by an integrated pipette tip device,including:

engaging a dispensing device with a device of any one of embodiments A1to A22,

drawing a fluid into the pipette tips of the integrated pipette tipdevice, and

dispensing the fluid from the pipette tips.

B2. The method of embodiment B1, which includes ejecting the integratedpipette tip device after the fluid is ejected from the pipette tips.

C1. An integrated pipette tip device, including:

a substantially flat card including a first surface and an opposingsecond surface, which card includes a plurality of apertures, eachaperture defining the opening of a channel traversing the thickness ofthe card;

which card includes a plurality of integrated pipette tips, each ofwhich pipette tips including a distal region that effectively extendsfrom the second surface of the card and is concentric with one aperture;and

which card includes a plurality of bores, each of which bores having anopening on the first surface of the card located at the intersection offour adjacent apertures, and which bores extend through at least aportion of the thickness of the card.

C2. The device of embodiment C1, wherein the thickness of the cardbetween the first surface and the second surface is about 0.5 to about 5millimeters.

C3. The device of embodiment C1 or C2, wherein the first surface of thecard includes one or more depressions, each of with depressionssurrounds one aperture of the card, and each of which depressions isconcentric with the aperture.

C4. The device of any one of embodiments C1 to C3, wherein the firstsurface of the card includes one or more protrusions, each of withprotrusions surrounds one aperture of the card, and each of whichprotrusions is concentric with the aperture.

C5. The device of embodiment C4, wherein the protrusion includes aprotrusion surface parallel to the first surface of the card, whichprotrusion surrounds a depression depressed from the protrusion surface,which depression surrounds one of the apertures of the card, and whichprotrusion is concentric with the depression and the aperture.C6. The device of any one of embodiments C3 to C5, which includes aplurality of depressions or a plurality of protrusions, or a pluralityof depressions and a plurality of protrusions.C7. The device of embodiment C6, wherein each aperture of the card iseffectively surrounded by one depression or one protrusion, or onedepression and one protrusion.C8. The device of any one of embodiments C3 to C7, wherein theprotrusions are annular protrusions.C9. The device of any one of embodiments C3 to C8, wherein thedepressions are annular depressions.C10. The device of any one of embodiments C1 to C9, wherein the distalregions of the pipette tips are in connection with the second surface.C11. The device of any one of embodiments C1 to C10, further including aplurality of dispenser sealing members, each of which dispenser sealingmembers including an opening in effective association with one channelof the card.C12. The device of embodiment C11, wherein the sealing member extendsfrom the second surface of the card and the distal region of eachpipette tip extends from the sealing member.C13. The device of embodiment C11, wherein the sealing member isconnected to the first surface of the card.C14. The device of embodiment C11, wherein the sealing member isconnected to or is seated in a protrusion surface.C15. The device of embodiment C11, wherein the sealing member isconnected to or is seated in a depression.C16. The device of any one of embodiments C13 to C15, wherein eachsealing member includes a flange surrounding the outer perimeter of thesealing member.C17. The device of any one of embodiments C11 to C16, wherein theexterior surface of the sealing member includes no sealing member ribs,no sealing member depressions, sealing member ribs, sealing memberdepressions or a combination thereof.C18. The device of embodiment C17, wherein the sealing member includesno sealing member ribs and no sealing member depressions.C19. The device of embodiment C17, wherein the sealing member ribs orsealing member depressions are parallel to an axis extending from theaperture of the card to the distal region of the pipette tip.C20. The device of embodiment C17 or C19, wherein the sealing memberribs include first ribs and second ribs, which first ribs and secondribs alternate along the circumference of the exterior surface of thesealing member, which first ribs are of a first thickness and whichsecond ribs are of a second thickness, and which first thickness isdifferent than the second thickness.C21. The device of any one of embodiments C17, C19 and C20, wherein thesealing member includes sealing member ribs, sealing member depressionsor a combination thereof, and wherein one or more of the ribs ordepressions contact the flange.C22. The device of any one of embodiments C11 to C21, wherein thesealing member is an annular sealing member.C23. The device of any one of embodiments C11 to C22, wherein thesealing member includes an exterior wall that is substantially verticalto the first surface of the card or the second surface of the card.C24. The device of any one of embodiments C11 to C23, wherein thesealing member includes a flexible material not present in the card orin the pipette tips.C25. The device of any one of embodiments C11 to C23, wherein thesealing member contains the same material as the card and the pipettetips.C26. The device of any one of embodiments C1 to C25, further including aplurality of pipette tip support ribs, each of which pipette tip supportribs is in connection with a pipette tip and the second surface of thecard.C27. The device of embodiment C26, wherein each pipette tip support ribis in contact with the distal region of a pipette tip.C28. The device of embodiment C26 or C27, wherein each pipette tipsupport rib is in contact with two pipette tips.C29. The device of embodiment C26 or C27, wherein each pipette tipsupport rib is in contact with one pipette tip and no other pipette tip.C30. The device of any one of embodiments C26 to C29, wherein thepipette tip support rib is in contact with a sealing member extendingfrom the second surface of the card.C31. The device of any one of embodiments C1 to C30, wherein the boresextend through the entire thickness of the card.C32. The device of any one of embodiments C1 to C31, wherein the openingof each of the bores is substantially square shaped or diamond shaped.C33. The device of embodiment C32, wherein each side of the squareshaped or diamond shaped opening is a curved side.C34. The device of embodiment C33, wherein each aperture of the card iscircular and the radius of curvature of each curved side of each bore isgreater than, and substantially follows, the radius of curvature of thecircular aperture.C35. The device of any one of embodiments C1 to C34, wherein the firstsurface is substantially flat and includes no protrusions and no sealingmembers.C36. The device of embodiment C35, wherein the first surface includes nodepressions.C37. The device of embodiment C35, wherein the first surface includesdepressions, each depression surrounding one aperture of the card.D1. An integrated pipette tip device, including:

a substantially flat card including a first surface and an opposingsecond surface, which card includes a plurality of apertures, eachaperture defining the opening of a channel traversing the thickness ofthe card;

which card includes a plurality of integrated pipette tips, each ofwhich pipette tips including a distal region that effectively extendsfrom the second surface of the card and is concentric with one aperture;and

which card includes a plurality of dispenser sealing members, each ofwhich sealing members including an opening in effective association withone channel of the card, and each of which sealing members (i) is inconnection with the second surface of the card and the distal region ofa pipette tip, or (ii) is in effective connection with the first surfaceof the card and includes one or more sealing member ribs, one or moresealing member depressions, a flange, a flexible material not present inthe card or pipette tips, or combination thereof.

D2. The device of embodiment D1, wherein the thickness of the cardbetween the first surface and the second surface is about 0.5 to about 5millimeters.

D3. The device of embodiment D1 or D2, wherein the first surface of thecard includes one or more depressions, each of with depressionssurrounds one aperture of the card, and each of which depressions isconcentric with the aperture.

D4. The device of any one of embodiments D1 to D3, wherein the firstsurface of the card includes one or more protrusions, each of withprotrusions surrounds one aperture of the card, and each of whichprotrusions is concentric with the aperture.

D5. The device of embodiment D4, wherein the protrusion includes aprotrusion surface parallel to the first surface of the card, whichprotrusion surrounds a depression depressed from the protrusion surface,which depression surrounds one of the apertures of the card, and whichprotrusion is concentric with the depression and the aperture.D6. The device of any one of embodiments D3 to D5, which includes aplurality of depressions or a plurality of protrusions, or a pluralityof depressions and a plurality of protrusions.D7. The device of embodiment D6, wherein each aperture of the card iseffectively surrounded by one depression or one protrusion, or onedepression and one protrusion.D8. The device of any one of embodiments D3 to D7, wherein theprotrusions are annular protrusions.D9. The device of any one of embodiments D3 to D8, wherein thedepressions are annular depressions.D10. The device of any one of embodiments D1 to D9, wherein the distalregions of the pipette tips are in connection with the second surface.D11. The device of any one of embodiments D1 to D10, wherein the sealingmember is an annular sealing member.D12. The device of any one of embodiments D1 to D11, wherein the sealingmember extends from the second surface of the card and the distal regionof each pipette tip extends from the sealing member.D13. The device of any one of embodiments D1 to D11, wherein the sealingmember is connected to the first surface of the card.D14. The device of any one of embodiments D1 to D11, wherein the sealingmember is connected to or is seated in a protrusion surface.D15. The device of any one of embodiments D1 to D11, wherein the sealingmember is connected to or is seated in a depression.D16. The device of any one of embodiments D13 to D15, wherein eachsealing member includes a flange surrounding the outer perimeter of thesealing member.D17. The device of embodiment D12, wherein the exterior surface of thesealing member includes no sealing member ribs, no sealing memberdepressions, sealing member ribs, sealing member depressions or acombination thereof.D18. The device of embodiment D17, wherein the sealing member includesno sealing member ribs and no sealing member depressions.D19. The device of any one of embodiments D1 to D17, wherein the sealingmember ribs or sealing member depressions are parallel to an axisextending from the aperture of the card to the distal region of thepipette tip.D20. The device of any one of embodiments D1 to D17 and D19, wherein thesealing member ribs include first ribs and second ribs, which first ribsand second ribs alternate along the circumference of the exteriorsurface of the sealing member, which first ribs are of a first thicknessand which second ribs are of a second thickness, and which firstthickness is different than the second thickness.D21. The device of any one of embodiments D1 to D17, D19 and D20,wherein the sealing member includes sealing member ribs, sealing memberdepressions or a combination thereof, and wherein one or more of theribs or depressions contact the flange.D22. The device of any one of embodiments D1 to D21, wherein the sealingmember includes an exterior wall that is substantially vertical to thefirst surface of the card or the second surface of the card.D23. The device of any one of embodiments D1 to D23, wherein the sealingmember includes a flexible material not present in the card or in thepipette tips.D24. The device of any one of embodiments D1 to D23, wherein the sealingmember contains the same material as the card and the pipette tips.D25. The device of any one of embodiments D1 to D24, further including aplurality of pipette tip support ribs, each of which pipette tip supportribs is in connection with a pipette tip and the second surface of thecard.D26. The device of embodiment D25, wherein each pipette tip support ribis in contact with the distal region of a pipette tip.D27. The device of embodiment D25 or D26, wherein each pipette tipsupport rib is in contact with two pipette tips.D28. The device of embodiment D25 or D26, wherein each pipette tipsupport rib is in contact with one pipette tip and no other pipette tip.D29. The device of any one of embodiments D25 to D28, wherein thepipette tip support rib is in contact with a sealing member extendingfrom the second surface of the card.D30. The device of any one of embodiments D1 to D29, including aplurality of bores, each of which bores having an opening on the firstsurface of the card located at the intersection of four adjacentapertures, and which bores extend through at least a portion of thethickness of the card.D31. The device of embodiment D30, wherein the bores extend through theentire thickness of the card.D32. The device of embodiment D30 or D31, wherein the opening of each ofthe bores is substantially square shaped or diamond shaped.D33. The device of embodiment D32, wherein each side of the squareshaped or diamond shaped opening is a curved side.D34. The device of embodiment D33, wherein each aperture of the card iscircular and the radius of curvature of each curved side of each bore isgreater than, and substantially follows, the radius of curvature of thecircular aperture.D35. The device of any one of embodiments D1 to D34, wherein the firstsurface is substantially flat and includes no protrusions and no sealingmembers.D36. The device of embodiment D35, wherein the first surface includes nodepressions.D37. The device of embodiment D35, wherein the first surface includesdepressions, each depression surrounding one aperture of the card andconcentric with the aperture of the card.E1. An integrated pipette tip device, including:

a substantially flat card including a first surface and an opposingsecond surface, which card includes a plurality of apertures, eachaperture defining the opening of a channel traversing the thickness ofthe card;

which card includes a plurality of integrated pipette tips, each ofwhich pipette tips including a distal region that effectively extendsfrom the second surface of the card and is concentric with one aperture;and

which card includes a plurality of pipette tip support ribs, each ofwhich pipette tip support ribs is in connection with one pipette tip andthe second surface of the card.

E2. The device of embodiment E1, wherein the thickness of the cardbetween the first surface and the second surface is about 0.5 to about 5millimeters.

E3. The device of embodiment E1 or E2, wherein the first surface of thecard includes one or more depressions, each of with depressionssurrounds one aperture of the card, and each of which depressions isconcentric with the aperture.

E4. The device of any one of embodiments E1 to E3, wherein the firstsurface of the card includes one or more protrusions, each of withprotrusions surrounds one aperture of the card, and each of whichprotrusions is concentric with the aperture.

E5. The device of embodiment E4, wherein the protrusion includes aprotrusion surface parallel to the first surface of the card, whichprotrusion surrounds a depression depressed from the protrusion surface,which depression surrounds one of the apertures of the card, and whichprotrusion is concentric with the depression and the aperture.E6. The device of any one of embodiments E3 to E5, which includes aplurality of depressions or a plurality of protrusions, or a pluralityof depressions and a plurality of protrusions.E7. The device of embodiment E6, wherein each aperture of the card iseffectively surrounded by one depression or one protrusion, or onedepression and one protrusion.E8. The device of any one of embodiments E3 to E7, wherein theprotrusions are annular protrusions.E9. The device of any one of embodiments E3 to E8, wherein thedepressions are annular depressions.E10. The device of any one of embodiments E1 to E9, wherein the distalregions of the pipette tips are in connection with the second surface.E11. The device of any one of embodiments E1 to E10, further including aplurality of dispenser sealing members, each of which dispenser sealingmembers including an opening in effective association with one channelof the card.E12. The device of embodiment E11, wherein the sealing member extendsfrom the second surface of the card and the distal region of eachpipette tip extends from the sealing member.E13. The device of embodiment E11, wherein the sealing member isconnected to the first surface of the card.E14. The device of embodiment E11, wherein the sealing member isconnected to or is seated in a protrusion surface.E15. The device of embodiment E11, wherein the sealing member isconnected to or is seated in a depression.E16. The device of any one of embodiments E13 to E15, wherein eachsealing member includes a flange surrounding the outer perimeter of thesealing member.E17. The device of any one of embodiments E11 to E16, wherein theexterior surface of the sealing member includes no sealing member ribs,no sealing member depressions, sealing member ribs, sealing memberdepressions or a combination thereof.E18. The device of embodiment E17, wherein the sealing member includesno sealing member ribs and no sealing member depressions.E19. The device of embodiment E17, wherein the sealing member ribs orsealing member depressions are parallel to an axis extending from theaperture of the card to the distal region of the pipette tip.E20. The device of embodiment E17 or E19, wherein the sealing memberribs include first ribs and second ribs, which first ribs and secondribs alternate along the circumference of the exterior surface of thesealing member, which first ribs are of a first thickness and whichsecond ribs are of a second thickness, and which first thickness isdifferent than the second thickness.E21. The device of any one of embodiments E17, E19 and E20, wherein thesealing member includes sealing member ribs, sealing member depressionsor a combination thereof, and wherein one or more of the ribs ordepressions contact the flange.E22. The device of any one of embodiments E11 to E21, wherein thesealing member is an annular sealing member.E23. The device of any one of embodiments E11 to E22, wherein thesealing member includes an exterior wall that is substantially verticalto the first surface of the card or the second surface of the card.E24. The device of any one of embodiments E11 to E23, wherein thesealing member includes a flexible material not present in the card orin the pipette tips.E25. The device of any one of embodiments E11 to E23, wherein thesealing member contains the same material as the card and the pipettetips.E26. The device of any one of embodiments E1 to E25, wherein eachpipette tip support rib is in contact with the distal region of apipette tip.E27. The device of any one of embodiments E1 to E26, wherein eachpipette tip support rib is in contact with two pipette tips.E28. The device of any one of embodiments E1 to E26, wherein eachpipette tip support rib is in contact with one pipette tip and no otherpipette tip.E29. The device of any one of embodiments E1 to E28, wherein the pipettetip support rib is in contact with a sealing member extending from thesecond surface of the card.E30. The device of any one of embodiments E1 to E29, including aplurality of bores, each of which bores having an opening on the firstsurface of the card located at the intersection of four adjacentapertures, and which bores extend through at least a portion of thethickness of the card.E31. The device of any one of embodiments E1 to E30, wherein the boresextend through the entire thickness of the card.E32. The device of any one of embodiments E1 to E31, wherein the openingof each of the bores is substantially square shaped or diamond shaped.E33. The device of embodiment E32, wherein each side of the squareshaped or diamond shaped opening is a curved side.E34. The device of embodiment E33, wherein each aperture of the card iscircular and the radius of curvature of each curved side of each bore isgreater than, and substantially follows, the radius of curvature of thecircular aperture.E35. The device of any one of embodiments E1 to E34, wherein the firstsurface is substantially flat and includes no protrusions and no sealingmembers.E36. The device of embodiment E35, wherein the first surface includes nodepressions.E37. The device of embodiment E35, wherein the first surface includesdepressions, each depression surrounding one aperture of the card.E38. The device of any one of embodiments C1 to C37, D1 to D37 or E1 toE37, wherein the device includes 384 or more integrated pipette tips.E39. The device of embodiment A38, wherein the device includes 1536integrated pipette tips.E40. The device of any one of embodiments C1 to C37, D1 to D37 or E1 toE39, wherein the card and pipette tips include a moldable plastic.E41. The device of embodiment D40, wherein the plastic includes one ormore of polypropylene (PP), polyethylene (PE), high-densitypolyethylene, low-density polyethylene, polyethylene teraphthalate(PET), polyvinyl chloride (PVC), polyethylenefluoroethylene (PEFE),polystyrene (PS), high-density polystyrene, acrylnitrile butadienestyrene copolymers, or a combination of two or more of the foregoing.E42. The device of embodiment E41, wherein the plastic includes PE.F1. A device of any one of embodiments C1 to C37, D1 to D37 or E1 to E42in sealing connection with a gasket, which gasket includes aperturesconcentrically aligned with the apertures in the device, which gasket isrelatively more resilient than the card of the device, and the surfaceof the gasket in connection with the first surface of the card coversabout 80% or more of the first surface of the card.F2. The device of embodiment F1, wherein the gasket includes annulargasket protrusions surrounding the gasket apertures.F3. The device of embodiment F2, wherein each gasket protrusions isconfigured to sealingly engage an inner surface of one card aperture.F4. The device of embodiment F2, wherein the card includes annular carddepressions surrounding the card apertures, which card depressions areconcentric with the card apertures and each of which card depressions isconfigured to sealingly engage with one gasket protrusion.F5. The device of embodiment F1, wherein the card includes annular cardprotrusions extending from the first surface, which card protrusionssurround the card apertures and are concentric with the card apertures.F6. The device of embodiment F5, wherein each of the card protrusions isconfigured to sealingly engage with an inner surface of one gasketaperture.F7. The device of embodiment F5, wherein the gasket includes annulargasket depressions surrounding the gasket apertures, which gasketdepressions are concentric with the gasket apertures and each of whichgasket depressions is configured to sealingly engage with one cardprotrusion.F8. The device of any one of embodiments F1 to F7, wherein the surfaceof the gasket in connection with the first surface of the card coversabout 90% or more of the first surface of the card.F9. The device of embodiment F6, wherein the surface of the gasket inconnection with the first surface of the card covers about 95% or moreof the first surface of the card.F10. The device of embodiment F9, wherein the surface of the gasket inconnection with the first surface of the card covers about 100% or moreof the first surface of the card.F11. The device of any one of embodiments F1 to F10, wherein the gasketincludes a moldable thermoplastic elastomer.F12. The device of any one of embodiments F1 to F11, wherein the gasketis substantially flat.G1. A method for dispensing a fluid by an integrated pipette tip device,including:

engaging a dispensing device with a device of any one of embodiments C1to C37, D1 to D37, E1 to E42, and F1 to F12,

drawing a fluid into the pipette tips of the integrated pipette tipdevice, and

dispensing the fluid from the pipette tips.

G2. The method of embodiment G1, which includes ejecting the integratedpipette tip device after the fluid is ejected from the pipette tips.

H1. A mold for manufacturing an integrated pipette tip device of any oneof embodiments C1 to C37, D1 to D37, or E1 to E42.

The entirety of each patent, patent application, publication anddocument referenced herein hereby is incorporated by reference. Citationof the above patents, patent applications, publications and documents isnot an admission that any of the foregoing is pertinent prior art, nordoes it constitute any admission as to the contents or date of thesepublications or documents.

Modifications may be made to the foregoing without departing from thebasic aspects of the technology. Although the technology has beendescribed in substantial detail with reference to one or more specificembodiments, those of ordinary skill in the art will recognize thatchanges may be made to the embodiments specifically disclosed in thisapplication, yet these modifications and improvements are within thescope and spirit of the technology.

The technology illustratively described herein suitably may be practicedin the absence of any element(s) not specifically disclosed herein.Thus, for example, in each instance herein any of the terms “including,”“consisting essentially of,” and “consisting of” may be replaced witheither of the other two terms. The terms and expressions which have beenemployed are used as terms of description and not of limitation, and useof such terms and expressions do not exclude any equivalents of thefeatures shown and described or portions thereof, and variousmodifications are possible within the scope of the claimed technology.The term “a” or “an” can refer to one of or a plurality of the elementsit modifies (e.g., “a reagent” can mean one or more reagents) unless itis contextually clear either one of the elements or more than one of theelements is described. The term “about” as used herein refers to a valuewithin 10% of the underlying parameter (i.e., plus or minus 10%), anduse of the term “about” at the beginning of a string of values modifieseach of the values (i.e., “about 1, 2 and 3” is about 1, about 2 andabout 3). For example, a weight of “about 100 grams” can include weightsbetween 90 grams and 110 grams. Ranges presented herein includeintermediate values (e.g., a range of between 80% to 90% includes basisfor about 86%, for example). Thus, it should be understood that althoughthe present technology has been specifically disclosed by representativeembodiments and optional features, modification and variation of theconcepts herein disclosed may be resorted to by those skilled in theart, and such modifications and variations are considered within thescope of this technology.

Embodiments of the technology are set forth in the claim(s) thatfollow(s).

What is claimed is:
 1. An integrated pipette tip device, comprising: asubstantially flat card comprising a first surface and an opposingsecond surface, which card comprises a plurality of apertures, eachaperture defining the opening of a channel traversing the thickness ofthe card; which card comprises a plurality of pipette tips integratedwith and connected to the card, each of which pipette tips comprising adistal region that effectively extends from the second surface of thecard and is concentric with one aperture; which card comprises aplurality of bores, each of which bores having an opening on the firstsurface of the card located at the intersection of four adjacentapertures, and which bores extend through at least a portion of thethickness of the card; and a plurality of dispenser sealing members,each of which dispenser sealing members comprising an opening ineffective association with one channel of the card.
 2. The device ofclaim 1, wherein each of the sealing members comprises a flangesurrounding the outer perimeter of the sealing member.
 3. The device ofclaim 1, wherein the exterior surface of each of the sealing membercomprises no sealing member ribs, no sealing member depressions, sealingmember ribs, sealing member depressions or a combination thereof.
 4. Thedevice of claim 1, wherein each of the sealing members comprises a wallthat is substantially vertical to the first surface of the card or thesecond surface of the card.
 5. The device of claim 1, wherein each ofthe sealing members comprises a flexible material not present in thecard or in the pipette tips.
 6. The device of claim 1, wherein each ofthe sealing members contains the same material as the card and thepipette tips.
 7. The device of claim 1, wherein each pipette tip supportrib is in connection with two pipette tips.
 8. The device of claim 1,wherein each pipette tip support rib is in connection with one pipettetip and no other pipette tip.
 9. The device of claim 1, wherein eachpipette tip support rib is in contact with a sealing member extendingfrom the second surface of the card.
 10. The device of claim 1, whereinthe opening of each of the bores is substantially square shaped orsubstantially diamond shaped.
 11. The device of claim 10, wherein eachside of the substantially square shaped opening or substantially diamondshaped opening is a curved side.
 12. The device of claim 11, whereineach aperture of the card is circular and the radius of curvature ofeach curved side of each bore is greater than, and substantiallyfollows, the radius of curvature of the circular aperture.
 13. Thedevice of claim 1, wherein the first surface is substantially flat andcomprises no protrusions and no sealing members.
 14. The device of claim1, wherein the card and pipette tips are molded with one another. 15.The device of claim 1, wherein the thickness of the card between thefirst surface and the second surface is about 0.5 to about 5millimeters.
 16. The device of claim 15, wherein the thickness of thecard between the first surface and the second surface is about 0.5 toabout 0.9 millimeters.
 17. The device of claim 1, further comprising aplurality of pipette support ribs.
 18. The device of claim 17, whereineach of the pipette tip support ribs is in contact with the distalregion of a pipette tip and the second surface of the card.
 19. Anintegrated pipette tip device, comprising: a substantially flat cardcomprising a first surface and an opposing second surface, which cardcomprises a plurality of apertures, each aperture defining the openingof a channel traversing the thickness of the card; which card comprisesa plurality of pipette tips integrated with and connected to the card,each of which pipette tips comprising a distal region that effectivelyextends from the second surface of the card and is concentric with oneaperture; which card comprises a plurality of bores, each of which boreshaving an opening on the first surface of the card located at theintersection of four adjacent apertures, and which bores extend throughat least a portion of the thickness of the card and at least about onethird of the card thickness in the bore is removed; and a plurality ofdispenser sealing members, each of which dispenser sealing memberscomprising an opening in effective association with one channel of thecard.
 20. An integrated pipette tip device, comprising: a substantiallyflat card comprising a first surface and an opposing second surface,which card comprises a plurality of apertures, each aperture definingthe opening of a channel traversing the thickness of the card; whichcard comprises a plurality of pipette tips integrated with and connectedto the card, a plurality of pipette tip support ribs, each of whichpipette tips comprising a distal region that effectively extends fromthe second surface of the card and is concentric with one aperture andwherein each pipette tip support rib extends from the second surface ofthe card to about three quarters of the length of the distal portion ofeach pipette tip; which card comprises a plurality of bores, each ofwhich bores having an opening on the first surface of the card locatedat the intersection of four adjacent apertures, and which bores extendthrough at least a portion of the thickness of the card; and a pluralityof dispenser sealing members, each of which dispenser sealing memberscomprising an opening in effective association with one channel of thecard.